The activated macrophage has been found to be a major effector of both specific immunologic and non-specific resistance to tumors. Further, the metabolic functions of macrophages have been shown to differ dependng on whether they are "activated" by such immunomodulators as C. parvum or pyran, stimulated (elicited) by inoculation with sterile inflammatory agents such as thioglycollate or glycogen or are "normal" (unstimulated). The objectives of this proposal are: 1) to characterize the specific functional group requirements of synthetic polycarboxylic acid polymer immunopotentiators that stimulate the elicited and activated stages of macrophage maturation, 2) to develop these carboxylic acid polymer agents which can differentiate the different stages of macrophage maturation from the resting "normal" state to the activated state, characterized by tumoricidal activity, and 3) to determine the structure activity relationship between these synthetic polyanionic polymeric immunopotentiators and the resultant elicited and activated stages of macrophage response. Initial studies will involve screening the capacitiy of these polyanionic polymers to induce functional changes in macrophages which are associated with the "elicited" or "activated" state. As a measure of elicitation we will determine the ability of peritoneal macrophage from mice inoculated with specifically synthesized polyanions to secrete plasminogen activator and to pinocytize horseradish perosidase (HRP). As a measure of activation we will test for the presence of a newly described cell surface antigen associated with activated but not normal or elicited macrophages and observe the induction of selective cytotoxicity for tumor cells.